Cyclodextrins (CDs) are a class of non-toxic, water-soluble D-glucose based macrocycles with a hydrophobic cavity. CDs typically vary by the number of glucose units. Common members include α-CD (6 glucose units), β-CD (7 glucose units) and γ-CD (8 glucose units), with increasing cavity size. The varying cavity sizes offer increased utility in a wide variety of applications, particularly in drug delivery models. For example, CDs can be used to form “inclusion complexes” in which a drug is included and carried within the cavity. This can be used as a pharmaceutical excipient to improve drug water solubility, chemical stability, and removal of certain drug side effects (such as undesirable taste). CDs have also drawn interest in the cosmetic and food additives industries, in the design of artificial enzymes, gene delivery vehicles, sensors and novel supramolecular assemblies.
CDs can be native or chemically modified on either or both of their primary and/or secondary faces. Typically, an inclusion complex has lower water solubility than native CDs. Chemical modifications of CDs can change their physico-chemical properties. For example, adding a tosyl group on the primary face of the β-CD renders the molecule near insoluble at room temperature, while adding methyl groups at OH-6 and OH-2 positions significantly increases water solubility. The toxicity of the molecule can also be changed. Therefore, modification of the CD molecule may present certain advantages. However, chemical modification of CDs is typically difficult to achieve, often leading to the formation of a mixture of products that are difficult to separate.
Amphiphilic CDs have generated considerable interest. These can be obtained through the modification of one face of a CD molecule with aliphatic chains. Amphiphilic CDs behave like surfactants, but are generally more stable. They can self-assemble in water to form large organized entities such as micelles, liposomes and lipid bilayers, which can be used to “trap” molecules either in the CD cavity or in the hydrophobic zone formed by the lipophilic tails or in both areas. The trapped molecules can be drugs, food additives and the like. This can enhance delivery of the molecules to the desired end point. In organic solvents, amphiphilic CDs can form inversed micelles and other self-assembled systems.
Amphiphilic CDs are usually poorly water soluble but are generally soluble in some organic solvents. However, it can be difficult to dissolve them into water, even through diffusion. They tend to form very large aggregates and are unstable, causing them to precipitate out over time. This makes them difficult to use for a variety of applications, particularly where water solubility is crucial. Further, the nature of the chemical synthesis is particularly difficult, generating lower than desired yields and contaminated with unacceptable side products. In all CD molecules, there exist three types of hydroxyl groups attached to the C6, C2 and C3 positions of the D-glucopyranosyl unit. It is relatively straightforward to chemoselectively differentiate one hydroxyl group from another, but it is much more challenging to regioselectively differentiate between hydroxyl groups of the same type because of their identical chemical properties.
Therefore, there is a need for water soluble amphiphilic CDs which are suitable for use in commercial applications.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.